hyperthyroidism, thyrotoxicosis, grave disease, thyroid storm, pregnancy, high risk pregnancy, pregnancy complications, management of thyrotoxicosis and thyroid storm in pregnancy

1. Sheila F. Perillo, MD

2.  Thyroid disease is the second most common
endocrine disease affecting women of
reproductive age

3.  a generic term referring to a clinical and biochemical
state resulting in over-production of and exposure to
thyroid hormone
 Overt hyperthyroidism complicates approximately 2 in
1,000 pregnancies.

4.  Pregnant women with hyperthyroidism are at
increased risk for:
 spontaneous pregnancy loss
 congestive heart failure
 thyroid storm
 preterm birth
 Preeclampsia
 fetal growth restriction, and
 increased perinatal morbidity and mortality

5.  the most common cause of thyrotoxicosis in
pregnancy
 An autoimmune condition characterized by
production of thyroid-stimulating immunoglobulin
(TSI) and thyroid-stimulating hormone binding
inhibitory immunoglobulin (TBII)
facilitate the thyroid-stimulating hormone
(TSH) receptor in the mediation of thyroid
stimulation and inhibition

6.  Hyperthyroidism- thyrotoxicosis resulting from an
abnormally functioning thyroid gland.
 Thyroid storm- acute, severe exacerbation of
hyperthyroidism

7.  associated with hyperemesis gravidarum
 can be due to high levels of human chorionic
gonadotropin (hCG) resulting from molar pregnancy
 high hCG levels  TSH receptor stimulation and
temporary hypothyroidism
 rarely symptomatic
 treatment with antithyroxine drugs- not beneficial
 expectant management
 not associated with poor pregnancy outcomes

8.  Thyroxine (T4), the major secretory product of the
thyroid gland, is converted in peripheral tissues to
triiodothyronine (T3)
 T3- biologically active form
 T4- secretion is under the direct control of pituitary
TSH
 T4 and T3 are transported in the peripheral circulation
bound to thyroxine-binding globulin (TBG),
transthyretin (formerly called "prealbumin") and
albumin.
 Less than 0.05% of plasma T4, and less than 0.5% of
plasma T3, are unbound and able to interact with
target tissues

9.  20 weeks' gestation
 reduced hepatic clearance
 estrogen-induced change in the structure of TBG that
prolongs serum half-life
 plasma TBG increases 2.5 folds   25% to 45%
increase in serum total T4 (TT4) from a pregravid level
of 5 to 12 mg to 9 to 16 mg
** Total T3 (TT3) increases by about 30% in the first
trimester and by 50% to 65% later

10.  Pregnancy  increase in available protein transient
change in free T4 (FT4) and free thyroxine index (FTI)
in the first trimester (possibly related to an increase in
hCG)
 Increased concentrations of TSH  stimulate
restoration of the free serum T4 level, such that FT4
and FTI levels are generally maintained within the
normal non-pregnant range

11.  Increase in volume
 Echo structure remains unchanged (Plasma iodide
levels decrease in pregnancy due to fetal use of iodide
and increased maternal renal clearance)
 15% to 18% increase in size of the thyroid gland
 enlargement usually resolves after delivery
 not associated with abnormal thyroid function tests

12.  Mild hyperthyroidism:
 Fatigue
 increased appetite
 Vomiting
 Palpitations
 Tachycardia
 heat intolerance,
 Increased urinary
frequency
 Insomnia
 Emotional instability
 The suspicion increases if
patient has
 Tremor
 Nervousness
 frequent stools
 excessive sweating
 brisk reflexes
 muscle weakness
 goiter
 Hypertension
 weight loss.
 Grave's ophthalmopathy (stare,
lid lag and retraction,
exophthalmos)
 dermopathy (localized or
pretibial myxedema)

13.  Untreated hyperthyroidism poses considerable
maternal and fetal risks, including preterm delivery,
severe preeclampsia, heart failure, and thyroid storm

15.  - a hypermetabolic complication of hyperthyroidism:
 hyperpyrexia (temperature >41ºC)
 cardiovascular compromise (tachycardia out of
proportion to the fever, dysrhythmia, cardiac failure)
 gastrointestinal upset (diarrhea)
 central nervous system changes (restlessness,
nervousness, changed mental status, confusion, and
seizures).

16.  Thyroid storm is a clinical diagnosis, and treatment
should be initiated before confirmatory test results
are available.

17.  Other signs of thyrotoxicosis in any patient with
postpartum congestive heart failure:
 tachycardia
 severe hypertension
 central nervous system (CNS) features, such as coma
after cesarean section or seizures suggestive of
eclampsia
 Delay in diagnosis increase the risk of maternal
mortality

18.  Thyroid storm is usually seen in patients with poorly
controlled hyperthyroidism complicated by additional
physiologic stressors, such as infection, surgery,
thromboembolism, preeclampsia, and parturition

19.  CBC (Leukocytosis)
 Thyroid function test results
are consistent with
hyperthyroidism (elevated
FT4/FT3 and depressed TSH)
but they may not always
correlate with the severity of
the thyroid storm
 Baseline electrolyte
(occasionally hypercalcemia)
 Glucose
 Renal
 Liver function testing
(elevated hepatic enzymes)
 Coagulation studies
 CT or MRI of the brain
(unconscious patients,
signs of focal CNS signs)
 blood, uterine and wound
cultures (as appropriate)
 chest x-ray
 12-lead electrocardiogram
(ECG) and continuous
cardiac monitoring
 Pulse oximetry
 blood gas analysis

20.  Thyroid storm is a clinical diagnosis based on
severe signs of thyrotoxicosis:
 significant hyperpyrexia (>103ºF or >41ºC)
neuropsychiatric symptoms
 Tachycardia with a pulse rate exceeding 140 beats/min
 congestive heart failure
 Gastrointestinal symptoms (nausea and vomiting)
accompanied by liver compromise

21.  Obstetric intensive care unit (ICU)/ ICU that has
continuous fetal monitoring and can handle an
emergent delivery
 Therapy is designed to:
 Reduce the synthesis and release of thyroid hormone
 Remove thyroid hormone from the circulation and
increase the concentration of TBG
 Block the peripheral conversion of T4 to T3
 Block the peripheral actions of thyroid hormone
 Treat the complications of thyroid storm and provide
support
 Identify and treat potential precipitating conditions

22.  Supportive adjunctive care for the patient in thyroid storm
are:
 IV fluids and electrolytes
 Cardiac monitoring
 Consideration of pulmonary artery catheterization
(central hemodynamic monitoring to guide beta-blocker
therapy during hyperdynamic cardiac failure)
 Cooling measures: blanket, sponge bath, acetaminophen,
avoid salicylates (risk of increased T4). Acetaminophen
is the drug of choice
 Oxygen therapy (consider arterial line to follow serial
blood gases)
 Nasogastric tube

23.  Reduce synthesis of thyroid hormones:
 Thionamides : propylthiouracil (PTU)
 Methimazole)
 inhibit iodination of tyrosine -- leading to reduce
synthesis of thyroid hormones and block peripheral
conversion of T4 to T3
 can reduce the T3 concentration by 75%

24.  Iodide (Lugol's iodine, SSKI (Strong Solution of
Potassium Iodide), sodium iodide, orografin, or lithium
carbonate)
 inhibit proteolysis of thyroglobulin  block the
release of stored hormone
**Because one of the side effects is an initial increase in
production of thyroid hormone, it is therefore very
important to start PTU before you give iodides

25.  Glucocorticoids
 block release of stored hormone (as do iodides), and
peripheral conversion of T4 to T3 (as do thionamides)
They may also bolster adrenal function, and prevent
adrenal insufficiency

26.  PTU orally or via nasogastric tube, 300-800 mg loading dose
followed by 150-300 mg every 6 hours
 One hour after instituting PTU give: Sodium iodide, 500 mg every
8-12 hours or oral Lugol's solution, 30-60 drops daily in divided
doses.
 Iodides may be discontinued after initial improvement
 Give adrenal glucocorticoids (Hydrocortisone, 100 mg IV every 8
hour, or Prednisone, 60 mg PO every day, or
 Dexamethasone, 8 mg PO every day)
 Glucocorticoids may be discontinued after initial improvement

27.  Beta-blocker agents --
 Propranolol can be used to control autonomic symptoms
(especially tachycardia)
 Some effect on inhibition of peripheral conversion of T4 to T3,
but will not alter thyroid hormone release nor prevent thyroid
storm.
 Use with caution: it has a tendency to increase pulmonary
diastolic pressure, and cardiac failure is a frequent
presentation of thyroid storm
 Reserved for heart rates of 120 beats per minute or higher
 Propranolol, labetalol, and esmolol

28.  Propranolol,1-2 mg/min IV or dose sufficient to slow heart rate
to 90 bpm; or 20-80 mg PO or via nasogastric tube every 4-6
hourly
 Esmolol, a short-acting beta-acting antagonist given IV with a
loading dose of 250 to 500 µg/kg of body weight followed by a
continuous infusion at 50 to 100 µg/kg/min
 Echocardiogram and/or pulmonary artery catheter to help guide
management, especially in cardiac failure
 If patient has severe bronchospasm -- give 1-5 mg reserpine
every 4-6 hours or 1 mg/kg orally of guanethidine every 12
hours.

29.  Heart failure due to cardiomyopathy from excessive
thyroxine in women with uncontrolled
hyperthyroidism is more common in pregnant women
 Same treatment as that of thyroid storm
 Medical emergency
 Give phenobarbital to control restlessness
 Phenobarbital: 30 to 60 mg orally every 6-8 hours as
needed
 Plasmapheresis or peritoneal dialysis
 to remove circulating thyroid hormone
 reserved for patients who do not respond to conventional therapy
 Subtotal thyroidectomy (during second-trimester pregnancy)
or radioactive iodine (postpartum)
 for unsuccessful conventional therapy

30.  Most asymptomatic women should have a TSH and free
T4 performed approximately 6 weeks postpartum
 PTU and methimazole are excreted in breast milk
 PTU is largely protein bound and does not seem to pose
a significant risk to the breastfed infant
 Methimazole has been found in breastfed infants of
treated women in amounts sufficient to cause thyroid
dysfunction
 at low doses (10-20 mg/d) it does not seem to pose a major risk to
the nursing infant

31.  PTU
 first-line treatment for Grave's disease in pregnancy due
to lower risks of teratogenicity than methimazole.
 It crosses the human placenta and associated with fetal
hypothyroidism
 Cordocentesis is sometimes recommended to test fetal
thyroid function
 does not readily crosses membranes
 milk concentrations are quite low

32.  Methimazole (Thiamazole, Mercazole, Tapazole):
 Second-line treatment of Grave's disease
 crosses the human placenta and can induce fetal goiter
and even cretinism in a dose-dependent fashion
 commonly associated with fetal anomalies such as
aplasia cutis, esophageal atresia, and choanal atresia
 Long-term follow-up studies of exposed children:
 no deleterious effects on their thyroid function or physical
and intellectual development with doses up to 20 mg/d
 excreted in breast milk

33. The American College of Obstetricians and
Gynecologists (ACOG) recommends treatment for
women with a systolic blood pressure higher than
170 mmHg and/or diastolic blood pressure above
109 mmHg
There is no consensus whether lesser degrees of
hypertension require treatment during pregnancy
because antihypertensive therapy improves only
the maternal, not the fetal, outcome in women with
mild to moderate chronic hypertension

34.  Radioactive iodine (iodine-131; I-131):
 contraindicated in pregnant women
 cost-effective, safe, and reliable treatment for
hyperthyroidism in non-pregnant women
 ACOG recommendation: women should avoid pregnancy
for 4-6 months following treatment
 Detrimental effects on the thyroid of the developing
fetus as a result of I-131 treatment for thyrotoxicosis of
the mother in the first trimester of pregnancy are
reported.
 Breast-feeding should be avoided for at least 120 days
after treatment

35.  Thyroid storm
 a life-threatening condition, requiring early recognition and
aggressive therapy in an intensive care unit setting.
 During gestation, women with hyperthyroidism should have
their thyroid function checked every 3-4 weeks.
 Grave's disease represents the most common cause of
maternal hyperthyroidism during pregnancy
 Only 0.2% of gestations are complicated by thyroid storm and
more than 90% of cases are caused by Grave's disease
 Increased production of thyroid hormone occurs when
autoantibodies (thyroid-stimulating antibody [TSAb] --
formerly known as LATS [long-acting thyroid stimulator])
against TSH receptors -- acts as TSH agonists.

38.  Thyroid Storm: Critical Care In Obstetrics
 WHEC Practice Bulletin and Clinical Management
Guidelines for healthcare providers. Educational grant
provided by Women's Health and Education Center
(WHEC).
 Published: 2 June 2010